The structures of lens orystallins and mechanisms responsible for post-synthetic modifications observed in these long-lived proteins during aging and cataractogenesis have been investigated. Three distinct classes of human gamma-crystallin have been identified and isolated. All three species have been shown to undergo a similar pattern of age-related modification in net charge. Evidence supporting the hypothesis that lipid peroxidation is responsible for the initiation of cataract in diseases involving retinal degeneration has been generated from studies on the Royal College of Surgeions rat model. Investigation of the effects of activated states of oxygen on the lens suggests that under conditions of generation outside thelens, the hydroxyl radical, an extremely strong oxidant, is less damaging to the organ cultured lens than is hydrogen peroxide, a much weaker but longer-lived species.